Mechanochemistry of Cardiac Muscle

Norepinephrine increases myocardial contractility and myocardial oxygen consumption (MV · O 2 ). It is not clear whether these phenomena are directly proportional or whether there is a disproportionate increase in MV · O 2 , signifying either uncoupling of oxidative phosphorylation or a direct increase in oxidative metabolism. Accordingly, the direct conversion of chemical energy to mechanical work was studied in control and norepinephrine-treated right ventricular papillary muscles from cats. Production of adenosine triphosphate (ATP) was inhibited by iodoacetic acid and N 2 . After resting or performing variable amounts of work, the muscles were instantly frozen, and the total amount of chemical energy (∼P = creatine phosphate + ATP) used was correlated with work performed and the number of contractions. There was no change in either the initial stores of energy or in the basal rate of energy utilization following treatment with norepinephrine. However, norepinephrine-treated muscles performing isometric work used 115% as much ∼P as control muscles in only 59% as many contractions and while performing only 87% as much work. Regression analysis of these data confirmed that norepinephrine-treated muscles used a greater amount of ∼P than do control muscles. Thus the increase in contractility induced by norepinephrine results in an increase in the amount of chemical energy released disproportionate to the amount of work performed, and the "oxygen wasting" effect of norepinephrine on heart muscle results from the increased utilization of energy associated with an increased contractile state.